Scientists in Germany have turned human organs transparent and captured pictures of the complex cellular architecture inside, the latest advance in an effort to develop a new way to see inside our tissues.
The new work involved a three-pronged approach: stripping the pigment and fats from organs; capturing images of entire organs with a specially designed, larger microscope; and developing an algorithms to analyze those images and spit out maps labeled with specific cellular structures.
But outside experts said the technique — described in a paper published this month in Cell — will need more polishing before it might be ready for prime time as a new imaging method.
“The paper delivers impressive proof-of-concept demonstrations … [but] it still seems like early days” for broader use of the tool, said Katrin Amunts, a neuroscientist and director of the Institute for Neuroscience and Medicine at Forschungszentrum Juelich in Germany, who wasn’t involved in the research.
Currently, scientists can study organs in living individuals with the help of imaging tools such as MRI and CT scans. They can also study slices of tissue from organs obtained postmortem and, with the help of new technologies, piece pictures of those slices together into 3D images of an organ’s structures.
But Ali Ertürk, director of the Institute of Tissue Engineering and Regenerative Medicine at Ludwig Maximilians University of Munich and senior author of the new study, is hopeful that his new approach could one day offer a new way to study organs in even closer detail.
“With our technology, we can see every single cell in an entire human organ,” said Ertürk.
Ertürk and his colleagues started their work by hunting for chemicals that could clean out the pigments and fats in organs, which block light. Ertürk’s lab and other groups had been able to clear the color from mouse organs. But the chemicals that worked in mice didn’t work for human tissue, which grows stiffer as collagen and other molecules accumulate over time.
They eventually pinpointed a detergent dubbed CHAPS, which created tiny holes throughout organs. The scientists could then soak the organs in other solutions that rendered them transparent without damaging the tissue structure.
“It’s like converting milk into water. It becomes transparent,” Ertürk said.
Ertürk and his colleagues partnered with the German-based biotech company Miltenyi Biotec to design a fluorescent microscope big enough to fit an organ-sized tissue sample under the lens. The microscope works on a sample as big as a human kidney, but doesn’t work on larger organs, such as the brain, which Ertürk and his colleagues have also been able to turn transparent.
The pictures the microscope captured create another challenge: how to process and analyze the massive amount of data generated by imaging human tissue at the cellular level.
Ertürk and his team collaborated with researchers at Technical University of Munich to develop algorithms that could analyze the structure of the organs, including the blood vessels and individual cells. The algorithm was roughly as accurate at labeling cell types as a human identifying the structures manually.
“It’s a task that would take 100 years by hand, and now takes hours,” he said.
Taken together, the approach to clearing and imaging intact organs is called SHANEL. The technology is still in the early stages. Etürk and his colleagues are working to develop a larger microscope that can image larger organs. They are also continuing to sharpen the artificial intelligence arm of SHANEL, developing new algorithms for each internal structure they want to identify, whether that’s a neuron or a glial cell in the brain.
Amunts, the Forschungszentrum Juelich neuroscientist, said scientists need to carefully study how the process of chemically clearing an organ might affect specific types of tissue, particularly in different regions of the brain. The brain’s regions vary more widely than tissues in other organs, like the kidney. There’s also a need for more research into the accuracy of clearing approaches — and how they stack up to standard organ imaging methods, like looking at 3D images of brain slices.
“It remains to be demonstrated that the tissue-clearing approach presented in the paper reaches the same precision, reliability, and reproducibility that established [methods] have,” she said.
Ertürk is hopeful that SHANEL can be used in the future to generate 3D maps of human organs that offer new insight into their function, structure, and the role they play in disease. That could be a helpful tool in studying complex organs, such as the brain, experts said.
“For basic science studies on the brain’s structure, I think this can become a very valuable complementary method in the toolset of neuroscientists,” Amunts said.
In the long run, Ertürk wants to use those maps to 3D print organs that accurately replicate their natural counterparts, down to the cellular level. Doing so, in theory, could mean creating lab-grown organs that function — and potentially, could one day be used for transplants, though there’s far more research to be done before that becomes a possibility, Ertürk said.